This project has two closely related aims (1) to seek a better understanding of the evolutionary relationship of the primates through analysis of the structure and expression of the globin genes during embryonic and fetal development; and (2) to follow clues about the controlling gene elements that determine when genes are turned on and off during gestation by observing differences in the timing of gene expression in these closely related animals. The research focuses on the globin genes, since they undergo a well-characterized sequence of switches during gestation in humans, and the control (reversal) of these switches may have significant medical benefits in hematological diseases such as sickle cell anemias and thalassemia. Expression profiles in the two branches of simian primates, catarrhines (Old World Monkeys, hominoids) and platyrrhines (New World Monkeys), suggests that more than one step was involved in the evolutionary transition. We are (1) localizing fe tal-speci fic sequences within the human ( gene; (2) using the strategy called differential phylogenetic footprinting to identify specific base changes that may be responsible for the three different patterns of ( expression seen in nonanthropoid primates; and (3) documenting the in vivo expression patterns of ( genes in extant platyrrhine and catarrhine primates. This work has important implications for clarifying the mechanisms that control new patterns of gene expression as well as for the understanding of factors that regulate hemoglobin switching. Using samples from the University of Washington Primate Center, we have found that globin gene expression is very similar in M. nemestrina and in humans (1) the expression is fetal; (2) (1 is expressed to a much higher level than (2; and (3) the intergenic distance is 11 kb. FUNDING NIH grants HL33940 and RR00166 and NSF grant INT-9602913. Goodman, M., Porter, C.A., Czelusniak, J., Page, S.L., Schneider, H., Shoshani, J., Gunnell, G., and Groves, C.P. Toward a phylogenetic classification of primates based on DNA evidence complemented by fossil evidence. Mol. Phylogenet. & Evol. 9:585-598, 1998. Goodman, M. The Genomic Record of Humankind's Evolutionary Roots. Am. J. Hum. Genetics 64:31-39, 1999.